Date: Nov. 7, 2013
FOR IMMEDIATE RELEASE
New Report Recommends Data-Driven Approach Over Default Practices for Assessing Multiple Health Effects of Inorganic Arsenic
WASHINGTON – A draft plan by the U.S. Environmental Protection Agency that describes how the agency will assess the potential health effects of oral exposure to inorganic arsenic should take greater advantage of the robust data that exists on the chemical in order to reach the best evidence-based conclusions, says a new report from the National Research Council. While EPA's draft assessment plan includes improved approaches for evaluating evidence and conducting analyses, the Research Council report recommends alternative statistical approaches over EPA's current default methods for estimating risk.
EPA's Integrated Risk Information System (IRIS) assessments identify disease hazards and characterize associations with adverse health outcomes for a wide variety of chemicals. EPA asked the Research Council to review its draft plan for carrying out the IRIS assessment of inorganic arsenic and evaluate critical scientific issues in assessing the potential health effects of oral exposure to the chemical. The new Research Council report recommends how these issues could be addressed in an IRIS assessment; a second report will review the draft IRIS assessment, expected to be performed by EPA in 2014.
EPA's draft plan for carrying out the IRIS assessment includes a framework for categorizing different adverse health effects according to how strongly the evidence supports or suggests a causal relationship with inorganic arsenic exposure. The Research Council committee that wrote the report largely agreed with this approach and offered a starting point for prioritizing these health outcomes. The report lists lung, skin, and bladder cancer, ischemic heart disease, and skin lesions as priority outcomes for EPA to evaluate, followed by prostate and renal cancer, diabetes, non-malignant respiratory disease, pregnancy outcomes, and immune effects.
For adverse health effects with evidence of a causal or likely to be causal relationship with inorganic arsenic, EPA will conduct mode-of-action analyses, which describe the pathways that connect exposure with events that occur at the cellular level and then with a measureable adverse health outcome. These analyses in turn help to inform dose-response analyses, which describe the relationship between different levels of exposure and the resulting health effects. The committee supported EPA's plan to conduct dose-response analyses for all health end points deemed to have a clear or likely causal relationship with inorganic arsenic, in contrast to previous assessments that only addressed cancer end points.
While much of the older epidemiologic data are derived from populations exposed to relatively high exposures of inorganic arsenic, the Research Council committee believes that newer studies of exposures in the low to moderate range deserve considerable attention. A key objective of the EPA assessment should be to better characterize risk at lower exposures. Focusing on whether the data for levels at or near background concentrations of inorganic arsenic are adequate for dose-response modeling will be an important part of the assessment process, the report says.
The committee recommended that EPA develop risk estimates for both cancer and noncancer effects on which there is adequate epidemiologic evidence and then derive risk-specific doses -- estimates of the level of exposure associated with a given degree of risk. For those health effects where the data are inadequate for modeling at low levels, extrapolation down to lower levels of exposure will be necessary.
EPA proposed to use linear extrapolation as the default approach for modeling the dose-response curve below the range of observation. The committee instead proposed a data-driven strategy, where a model would be fit to the observed data and then used to extrapolate to a limited extent below the range of observation to estimate a potential dose response at lower levels. Fitting multiple models to the data could help improve the accuracy of the extrapolation and provide greater confidence in the risk estimate.
The committee also identified several factors that could affect susceptibility to inorganic arsenic, including life stage when exposure occurs, genetic factors, sex, nutritional deficiencies, health status, smoking or alcohol consumption, or exposures to mixtures of chemicals. Based on the degree of evidence concerning these vulnerability factors, consideration should be given to whether dose-response analyses should focus on the population as a whole or involve separate assessments for the susceptible groups, the report says. In particular, consideration should also be given to early-life exposure and the risk of adverse health effects later in life, the report adds. EPA’s current approach of assessing partial-lifetime exposures by prorating the risk equally regardless of age needs to be critically evaluated to determine whether it is appropriate for assessing inorganic arsenic.
The report's recommendations for improving EPA's plan for carrying out the assessment are specific to inorganic arsenic and may not be applicable to the assessment of other chemicals. Moreover, the report focuses only on health outcomes from oral exposure and does not consider inhalation or dermal exposure.
The study was sponsored by the U.S. Environmental Protection Agency. The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. They are private, independent nonprofit institutions that provide science, technology, and health policy advice under a congressional charter granted to NAS in 1863. The Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering. For more information, visit http://national-academies.org. A committee roster follows.
Lauren Rugani, Media Relations Officer
Rachel Brody, Media Relations Associate
Office of News and Public Information
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Report in Brief
Pre-publication copies of Critical Aspects of EPA's IRIS Assessment of Inorganic Arsenic: Interim Report are available from the National Academies Press on the Internet at http://www.nap.edu or by calling tel. 202-334-3313 or 1-800-624-6242. Reporters may obtain a copy from the Office of News and Public Information (contacts listed above).
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NATIONAL RESEARCH COUNCIL
Division on Earth and Life Studies
Board on Environmental Studies and Toxicology
Committee on Inorganic Arsenic
Joseph H. Graziano (chair)
Department of Environmental Health Sciences
Mailman School of Public Health
New York City
Louis Block Professor of Health Studies
Department of Health Studies
University of Chicago
Sandra J.S. Baird
Office of Research and Standards
Massachusetts Department of Environmental Protection
Department of Environmental and Occupational Health
Graduate School of Public Health
University of Pittsburgh
Hugh A. Barton
Associate Research Fellow
Gary P. Carlson
Professor Emeritus of Health Sciences
West Lafayette, Ind.
Mary E. Davis
Department of Physiology and Pharmacology
West Virginia University
Yvonne P. Dragan
Rebecca C. Fry
Department of Environmental Sciences and Engineering
University of North Carolina
Professor of Biostatistics
Department of Biostatistics
Virginia Commonwealth University
Gary L. Ginsberg
Division of Environmental and Occupational
Connecticut Department of Public Health
Department of Community and Family Medicine
Geisel School of Medicine
James S. MacDonald
Chrysalis Pharma Consulting LLC
Department of Environmental Health Sciences
Bloomberg School of Public Health
Johns Hopkins University
Marie E. Vahter
National Institute of Environmental Medicine
Robert O. Wright
Professor of Preventive Medicine
Mount Sinai School of Medicine
New York City
Susan N.J. Martel